Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, but we do not yet have any effective screening methods to detect these cancers. This knowledge gap is in part due to difficulties identifying oropharyngeal precursor lesions. However, several promising salivary and blood biomarkers have recently emerged that may be good markers of persistent oral HPV16 infection, the presumed pre-cursor to HPV-related oropharyngeal cancer. Given the increasing incidence of HPV-related oropharyngeal cancer, I propose to study the oral HPV continuum to answer the following 4 questions: 1) who is at high- risk for HPV-OPC and would benefit from screening, 2) What are the biologic and behavioral factors promoting oral HPV persistence and how can we reduce their effects, 3) how to optimally screen for persistent oral HPV16 infection and HPV-OPC, and 4) How to follow and treat people who screen positive for these biomarkers to prevent the development of HPV-related oropharyngeal cancer.